Scatterplots of LTL (standardized relative mean leukocyte telomere length) at follow-up in relation to the number of unemployment days in the preceding three years 1995–97.

<p>The lines indicate the LTL curves fitted to cubic function of unemployment days and the dashed lines their 95% confidence intervals.</p

Frequencies, percentages and prevalence ratios (with 95% confidence intervals, CI) of the participants belonging to the shortest decile of standardized relative mean leukocyte telomere length (LTL) at follow-up in relation to the categories of biological, socioeconomic, behavioural and medical covariates and exposure to unemployment days in the preceding three years.

<p>Frequencies, percentages and prevalence ratios (with 95% confidence intervals, CI) of the participants belonging to the shortest decile of standardized relative mean leukocyte telomere length (LTL) at follow-up in relation to the categories of biological, socioeconomic, behavioural and medical covariates and exposure to unemployment days in the preceding three years.</p

Unadjusted and adjusted association analyses of child and adult adiposity predictors of LTL.

<p>AR is adiposity rebound; LTL is leukocyte telomere length. WHR is waist-to-hip ratio, BMI is body mass index, calculated as weight (kg)/height (m)². BAI is body adiposity index, calculated as (hip circumference (cm))/((height(m)^1.5)−18). BMI <i>z-score</i> change was calculated separately in males and females as the difference between the <i>z-scores</i> of BMI at AR, and BMI at 31 years. The number of individuals in each analysis is given (N); those in adjusted analyses are slightly lower than corresponding unadjusted analyses due to missing data for one or more covariates.</p>a<p>Linear regression model adjusted for maternal parity, SES at birth, Smoking at 31 years, SES at 31 years, children at 31 years and qPCR plate. In addition to these potential confounders, the model was also adjusted for age at menarche in women.</p>b<p>% change in LTL per unit change in predictor variable.</p>c<p>Statistically significant <i>P_corrected</i> values are shown in <b>bold</b>. FDR <i>P_corrected</i> values were calculated after adjustment using the Benjamini-Hochberg procedure <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099133#pone.0099133-Aviv2" target="_blank">[34]</a>, which provides a correction for multiple testing.</p

Flow chart for inclusion of study participants.

<p>Flow chart for inclusion of study participants.</p

Location of c.76_98del; p. E26RfsX68 <i>CPE</i> mutation.

<p>A: Schematic overview of the exons of <i>CPE</i> (Refseq: NM_001873). Dark shaded areas are UTRs and light grey areas are coding regions. B: Human CPE protein (UniprotKB: P16870). Location of the E26RfsX68 mutation is shown by the red diagonally striped region. Arrow shows the location of Arg283Trp. SP, signalling peptide; PP, pro-peptide. C: Indicative chromatogram of the deletion in the proband and the normal wild-type sequence. The deletion is indicated in red. Amino acid changes caused by the frameshift are shown above the chromatogram.</p

CPE mRNA expression levels.

<p>Real time PCR analysis of <i>CPE</i> mRNA expression in blood samples from the proband (II.6), heterozygous sibling (II.5) and six controls. For controls mean ± SEM (standard error of the mean) is depicted. All analyses were conducted in triplicate.</p

Clinical features of proband with homozygous truncating <i>CPE</i> mutation.

<p>Photograph of proband carrying a homozygous truncating deletion of <i>CPE</i>. Specific written consent for the photograph and case details was obtained from proband and mother. At the time of examination, the proband had a weight of 130.2 kg and height of 1.59 m with body mass index (BMI) 51.5 kg/m². There was some intellectual disability, for example despite adequate schooling she was unable to read or write words. She had newly diagnosed type 2 diabetes mellitus with fasting glucose 383 mg/dL, 21.1 mmol/L; HbA1c 114 mmol/mol, 12.6%) and hypogonadotrophic hypogonadism with primary amenorrhea (serum oestradiol 78 pmol/L [post-menopausal range <100 pmol/L], 21.2 pg/mL; LH 2.7 IU/L, FSH 2.0 IU/L). Serum hormone analysis excluded other causes of amenorrhoea including polycystic ovary syndrome and hyperprolactinaemia (testosterone 1.2 nmol/L (normal <2.7), 0.35 ng/mL (normal <0.78); normal androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulphate (DHEAS), prolactin). There was no history of depression or anxiety.</p

Association results of index CRP loci (7–10) in Singaporean datasets.

<p>22 SNPs were genotyped or imputed and passed QC procedures in all 3 datasets and were combined in a meta-analysis (see Table S5 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067650#pone.0067650.s001" target="_blank">File S1</a> for full results). Significant results (p-value <0.05) in bold.</p><p>TAF: Test allele frequency. ^† Variants which were significant but not directionally consistent with previous European study (7).</p>*<p>Mean allele frequency from 3 SNP-chips used for the SP2 study. Q_pvalue <0.1 indicates between study heterogeneity.</p

Comparison of observed and expected association results for rs2794520 and CRVE in A) SP2, B) SiMES and C) SINDI datasets.

<p>Observed regression values presented in black and estimated values presented in gray. Regression models were adjusted for age and sex in SP2 and age, sex and population stratification (first 2 principal components in SiMES and first 3 principal components in SINDI only).</p

Clinical measures in SiMES, SP2 and SINDI datasets used in study.

*<p>Excluding 242 samples from SINDI, 190 samples from SiMES and 48 samples from SP2, respectively who had CRP values >10 mg/L.</p>†<p>hypertension defined as history of hypertension or SBP>140 mmHg or DBP>90 mmHg.</p>‡<p>diabetes defined as participants with a history of diabetes mellitus or fasting glucose levels ≥7.0 mmol/L in SP2 and HbA1c levels ≥6.5% in non-fasting blood samples and/or those with previous history in SiMES and SINDI.</p